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NCID > For Healthcare Professionals > Diseases and Conditions > Yellow Fever and other viral haemorrhagic fevers

Yellow Fever and other viral haemorrhagic fevers

Yellow Fever and other viral haemorrhagic fevers


Causative Agent

Yellow Fever Virus (YFV)

Incubation Period

3 - 6 days

Infectious Period

Initial 5 days of illness.


Vector-borne transmission occurs via bite of an infected mosquito, primarily Aedes or Haemogogus spp. Nonhuman and human primates are the main reservoirs of the virus; anthroponotic (human-to-vector-to-human) transmission occurs.

Three main transmission cycles:

  • The sylvatic (jungle) cycle involves transmission of the virus between non- human primates and mosquito species found in the forest canopy and subsequent transmission to humans when they encroach into the jungle during occupational and recreational activities.
  • The intermediate (savannah) cycle in Africa involves transmission of YFV from monkeys to hole-breeding Aedes spp to humans working or living in jungle border areas.
  • The urban cycle involves transmission of the virus between humans and urban mosquitoes, primarily Ae. aegypti.

Humans infected by YFV experience high levels of viraemia making blood-borne transmission possible (via transfusion, needle stick, and intravenous drug abuse)


Yellow fever occurs in sub-Saharan Africa and tropical South America, where it is endemic with intermittent epidemics. In Africa, natural immunity increases with age, thus infants and children are at greatest risk for disease.

The incidence world-wide has increased due to recurrent epidemics in several West African cities.

  • Suspect in a febrile traveller who has been to a YF endemic country during the preceding 6 days and has not been vaccinated against the disease.
  • The clinical spectrum of yellow fever includes subclinical infection; abortive non-specific febrile illness without jaundice; and life threatening illness with fever, jaundice, renal failure and hemorrhage. >
  • About 1 in 5 - 20 infections result in clinical disease with jaundice, the rest are abortive or subclinical.
  • Three phases of disease:
    • Early phase - Viremic stage characterised by fever, chills, headache, backache, myalgia, prostration with bradycardia, conjunctival injection and coated tongue.
    • Period of “remission” occurring over next several days with transient recovery and remission of fever lasting up to 48 hours. Patients with abortive infections recover at this stage. Approximately 15 percent of individuals infected with YFV enter the third stage of the disease.
    • Period of “intoxication” begins on the 3rd to the 6th day of infection with increasing systemic symptoms, jaundice, albuminuria, oliguria, haemorrhagic complications (black vomit), delirium, stupor, acidosis and shock.
  • Case-fatality rate is 20 - 50 % between the 7th and 10th day after onset.
  • The differential diagnoses are varied; viral hepatitis, leptospirosis, malaria, typhoid and other viral haemorrhagic fevers need to be excluded.

  • Leucopoenia, thrombocytopenia
  • Elevated direct bilirubin, transaminases, urea, creatinine
  • Hypoglycaemia
  • Specific diagnosis by:
    • viral isolation from blood or tissue specimens.
    • identification of viral antigen or nucleic acid in tissues (including liver) using immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) antigen capture, or polymerase chain reaction tests.
    • serological diagnosis by IgM antibody capture (ELISA), histo- immunochemistry or complement fixation tests (CFT).
Locally, a complement fixation test to the flaviviruses group can be done. Positive results in the appropriate clinical setting may be suggestive but not confirmatory.

A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. Call MOH Communicable Diseases Surveillance team at : 98171463 as soon as the diagnosis is suspected.

  • Suspected patients will be isolated at CDC. Treatment is symptomatic and supportive and directed at the management of the complications of YF.
  • There is no specific anti-viral therapy.

  • YF vaccine consists of a live attenuated virus preparation. A single subcutaneous injection of 0.5 ml of reconstituted vaccine offers protection for up to 10 years. The International Health Regulations require revaccination at intervals of 10 years. Recommended only for persons older than 9 months of age. It offers > 95% protection.
  • Any disembarking passenger suspected to be infected will be transferred immediately to the CDC for isolation.
  • During the acute phase of the infection, the patient should  be protected  from mosquito bites to avoid spread of the infection. Universal  precautions against blood/body fluids and sharps should be in place.
  • Epidemic control measures include mosquito control with special attention given to airports, hospitals and the homes and vicinity of the confirmed and suspected cases. All contacts and health personnel will need to be vaccinated and kept under surveillance.
  • The public and the World Health Organisation will be informed of all suspected and confirmed cases.


South/Central America and Caribbean

  • Angola
  • Benin
  • Burkina Faso
  • Burundi
  • Cameroon
  • Chad
  • Central African Republic
  • Congo
  • Côte d'Ivoire
  • Democratic Republic of the Congo
  • Ethiopia
  • Equatorial Guinea
  • Gabon
  • Gambia, The
  • Ghana
  • Guinea
  • Guinea-Bissau
  • Kenya
  • Liberia
  • Mali
  • Mauritania
  • Niger
  • Nigeria
  • Rwanda
  • São Tomé & Príncipe
  • Senegal
  • Sierra Leone
  • Somalia
  • Sudan
  • Tanzania
  • Togo
  • Uganda
  • Argentina
  • Bolivia
  • Brazil
  • Colombia
  • Ecuador
  • French Guiana
  • Guyana
  • Panama
  • Paraguay
  • Peru
  • Suriname
  • Trinidad & Tobago
  • Venezuela

Source: CDC Travel Information 2010 Yellow Book


  • Singapore requires a yellow fever vaccination certificate from travellers over one year of age who, within the preceding 6 days have been in or have passed through any of the countries partly or wholly endemic for yellow fever.
  • Yellow fever vaccination must be administered at a WHO-approved yellow fever vaccination centre.
  • After immunisation, an International Certificate of Vaccination is issued and is valid 10 days after vaccination to meet entry and exit requirements for all countries.
  • A country-by-country listing of Yellow Fever Vaccination Requirements is provided in: (1) the US Centers for Disease Control & Prevention (CDC) document “Comprehensive Yellow Fever Vaccination Requirements” under CDC Travel Information and; (2) the WHO International Travel and Heatlh (

Causative Agents

  • Filoviruses (including Ebola and Marburg viruses) Arenaviruses (including Lassa fever)
  • Bunyaviruses (including Rift Valley fever, Crimean-Congo haemorrhagic fever, and hantaviruses)
  • Flaviviruses (including dengue, yellow fever)

Comparison of Viral Haemorrhagic Fevers


n period


Mode of

Specific clinical features




Lassa Fever

6-21 days

Rural West Africa, Sierra Leone, Guinea, Liberia, Nigeria

Direct contact with infected rodents; person-to-person; inhalation of aerosol
from rodent urine

Inflammation of throat (with white exudates) and eye, encephalopathy, deafness, loss of

Serology, viral isolation

+/- ribavirin

Control of rodents, barrier nursing & surveillance of contacts

Rift Valley Fever

2-6 days

Sub-Saharan Africa, Egypt, Madagascar, and Mauritania, Kenya, Somalia, Tanzania and

Bites from infected arthropods; direct contact with infected animals; aerosols

Encephalitis, ocular disease

Serology, viral isolation, PCR

+/- ribavirin

Animal vaccination, protection & prevention of mosquito bites,
barrier nursing

Ebola and Marburg Fever

5-21 days

Republic of Congo, Côte d'Ivoire, Democratic Republic of Congo, Angola and possibly Zimbabwe

Direct contact with infected blood, secretions and organs; person-to- person

Maculopapular rash, jaundice, multi-organ failure

Serology, viral isolation, PCR


Barrier nursing

Crimean-Congo Haemorrhagic Fever

1-13 days

Endemic in many countries in Africa, Europe and Asia, and during 2001, cases or outbreaks have been recorded in Kosovo, Albania, Iran, Pakistan,
and South Africa.

Bites of infected ticks; direct contact with infected livestock

Tachycardia, hepatomegaly, lymphadenopathy, multi- organ failure

Serology, viral isolation, antigen detection, PCR

+/- ribavirin

Personal protective measures against tick bites & infected livestock, barrier nursing


  1. CDC Health Information for International Travel 2010. The Yellow Book: Available at Accessed Dec 2010.
  2. WHO Yellow Fever Fact Sheet. Available at Dec 2010.
  3. International Travel & Health. WHO, Geneva 2010. Available at Accessed Dec 2010.
  4. Barnett, ED. Yellow fever: epidemiology and prevention. Clin Infect Dis 2007; 44:850

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